Tigacil
Tigacil: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Tigacil
ATX code: J01AA12
Active ingredient: tigecycline (Tigecycline)
Manufacturer: Pfizer Ireland Pharmaceuticals (Ireland); Wyeth Medica Ireland (Ireland); Wyeth Parenterals Division Of Wyeth Holdings Corporation (Puerto Rico); Pateon Italy S.p. A. (Patheon Italia, SpA) (Italy); Wyeth Lederle Es.p. Hey. (Wyeth Lederle SpA) (Italy)
Description and photo update: 2018-27-11
Prices in pharmacies: from 20173 rubles.
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Tigacil is a tetracycline antibiotic.
Release form and composition
Dosage form - lyophilisate for preparation of solution for infusion: powder or porous mass of orange color (in colorless glass vials with a volume of 5 ml, 10 vials in a cardboard box and instructions for use of Tigacil).
One bottle contains:
- active substance: tigecycline - 50 mg;
- auxiliary components: sodium hydroxide, hydrochloric acid, lactose monohydrate.
Pharmacological properties
Pharmacodynamics
The active substance of Tigacil - tigecycline, is an antibiotic from the group of glycylcycline, which are structurally similar to tetracyclines. The mechanism of its action is explained by the ability to bind to the 30S-subunit of ribosomes and block the penetration of aminoacyl-tRNA molecules into the A (aminoacyl) -site of the ribosome, as a result of which protein translation in bacteria is inhibited and, as a consequence, the inclusion of amino acid residues in growing peptide chains is prevented.
Tigecycline is believed to have bacteriostatic activity. At a fourfold minimum inhibitory concentration (MIC) of the drug, a decrease in the number of colonies of Escherichia coli, Enterococcus spp. and Staphylococcus aureus by two orders of magnitude.
Tigecycline has a bactericidal effect against Haemophilus influenzae, Legionella pneumophila and Streptococcus pneumoniae.
Unlike tetracyclines, tigecycline is able to overcome two main mechanisms of resistance of pathological microorganisms, such as ribosomal protection and active excretion. In addition, its activity is not suppressed by modification of sensitive areas of the bacterial membrane, the action of β-lactamases (including extended spectrum β-lactamases), active elimination of the drug from the bacterial cell, or modification of the target of exposure (for example, topoisomerase or gyrase). Thus, tigecycline is characterized by a broad spectrum of antibacterial action. However, it does not have protection against the bacterial resistance mechanism in the form of active elimination from the cell, encoded by the chromosomes of Proteeae and Pseudomonas aeruginosa (MexXY-OprM efflux system).
There is no cross-resistance between tigecycline and most antibiotic groups.
Microorganisms of the genus Morganella spp., Proteus spp. and Providencia spp. less sensitive to tigecycline than Enterobacteriaceae. Some acquired resistance to tigecycline has been found in Enterobacter aerogenes, Enterobacter cloacae, and Klebsiella pneumoniae. The reduced sensitivity of bacteria to Tigacil is explained by the overexpression of the gene for nonspecific active excretion of AcrAB, which ensures the resistance of microorganisms to many drugs. There is evidence that the sensitivity to tigecycline is also reduced in Acinetobacter baumannii.
The European Antibiotic Susceptibility Testing Working Group (EUCAST) has established the following MIC control values (pathogen: sensitive concentrations; resistant concentrations):
- Enterococcus spp.: ≤ 0.25 mg / l; > 0.5 mg / l;
- Streptococcus spp., (Excluding S, pneumoniae): ≤ 0.25 mg / l; > 0.5 mg / l;
- Staphylococcus spp.: ≤ 0.5 mg / l; > 0.5 mg / l;
- Enterobacteriaceae: ≤ 1 mg / L *; > 2 mg / l;
- regardless of the type of pathogen: ≤ 0.25 mg / l; > 0.5 mg / l.
* In vitro activity of tigecycline is reduced against Morganella spp. and Proteus spp., Providencia spp.
For infections caused by the following microorganisms, there is no evidence of the effectiveness of tigecycline: Moraxella catarrhalis, Acinetobacter spp., Neisseria meningitidis, Haemophilus influenzae, Neisseria gonorrhoeae, Streptococcus pneumoniae, and other streptococci.
Regardless of the parameters of BMD, pharmacokinetic and pharmacodynamic parameters, the effectiveness of Tigacil is confirmed in intra-abdominal infections caused by anaerobic bacteria. Tigecycline has a wide range of minimum inhibitory concentrations for Clostridium spp. and Bacteroides spp., sometimes exceeding 2 mg / l.
For enterococcal infections, data on the clinical efficacy of the drug are limited. However, positive dynamics was confirmed in the treatment of polymicrobial intra-abdominal infections.
In certain bacterial species, the severity of acquired resistance may vary depending on time and geographic location.
Pseudomonas aeruginosa has intrinsic resistance to Tigacil.
The following species may develop acquired resistance: Morganella morganii, Acinetobacter baumannii, Stenotrophomonas maltophilia, Providencia spp., Burkholderia cepacia, Proteus spp.
The following bacteria are sensitive to the active substance Tigacil:
- gram-negative aerobic microorganisms: Moraxella catarrhalis, Aeromonas hydrophila, Peptostreptococcus micros, Peptostreptococcus spp. *, Citrobacter koseri, Citrobacter freundii *, Escherichia coli * (including strains that produce Clophin influenzae parafilfilus para, Haophilus influenzae, broad spectrum Haophilus influenzae para., Klebsiella pneumoniae * (including strains producing broad spectrum β-lactamase), Enterobacter cloacae *, Enterobacter aerogenes, Bacteroides fragilis group *, Legionella pneumophila, Klebsiella oxytoca *, Prevotella spp., Serratia marcescens;
- gram-positive aerobic microorganisms: Enterococcus gallinarum, Enterococcus faecalis (including vancomycin-resistant strains), Enterococcus casseliflavus, Enterococcus avium, Enterococcus faecalis * (including vancomycin-resistant strains, Sturealus aureus haphalococcus *, Streacloecoccus agurecoccus agurecoccus haptococcus * methicillin-susceptible strains), Staphylococcus epidermidis (including resistant and methicillin-susceptible strains), Streptococci viridans group, Streptococcus pyogenes *, Streptococcus anginosus * group (including S.anginosus, S.constellatus, S. pneumoniae), Streptococci pneumonia penicillin-resistant strains), Streptococcus pneumoniae * (penicillin-sensitive strains);
- atypical microorganisms: Chlamydia pneumoniae and Mycoplasma pneumoniae.
* Species that have demonstrated satisfactory sensitivity in clinical studies.
Pharmacokinetics
When administered intravenously (IV), tigecycline is characterized by 100% bioavailability.
At concentrations in the range of 0.1–1 μg / ml in vitro, the substance binds to plasma proteins by about 71–89%. It is quickly distributed in tissues. The equilibrium volume of distribution in the human body is 500-700 l (7-9 l / kg), which indicates extensive distribution outside the plasma and accumulation in tissues. There are no data on the ability of the drug to penetrate the blood-brain barrier.
The maximum equilibrium concentration of tigecycline in serum is: with 30-minute infusions - 866 ± 233 ng / ml, with 60-minute infusions - 634 ± 97 ng / ml.
The area under the concentration-time curve (AUC 0–12 h) is 2349 ± 850 ng × h / ml.
Less than 20% of tigecycline is metabolized. In urine and feces, mainly unchanged tigecycline is found, but tigecycline epimer, glucuronide and N-acetyl metabolite are also found.
Neither competitive nor irreversible inhibition of cytochrome P450 by tigecycline was found. The drug does not suppress metabolism mediated by isoenzymes CYP2D6, CYP2C9, CYP1A2, CYP3A4, CYP2C19, CYP2C8.
Approximately 59% of the received dose of tigecycline is excreted through the intestine (with a larger amount of unchanged substance entering the bile), 33% - by the kidneys. Additional routes of elimination are glucuronidation and elimination of unchanged tigecycline.
After intravenous infusion, the total clearance of the active substance of Tigacil is 24 l / h. Renal clearance is approximately 13% of the total.
Tigecycline demonstrates polyexponential elimination from serum. The average final serum half-life after administration of several doses of the drug is 42 hours, however, significant individual differences are possible.
Pharmacokinetics in special clinical situations:
- race and gender: the pharmacological parameters of tigecycline are independent of the race and gender of the patient;
- age: the pharmacokinetics of the drug in elderly patients does not differ significantly from that in other age groups, in patients under 18 years of age has not been studied;
- body weight: the higher the patient's body weight, the greater the difference in AUC and clearance of tigecycline, in particular in patients with a body weight above 125 kg, the AUC is 25% lower. Parameters in patients weighing over 140 kg are unknown;
- hepatic impairment: with mild liver dysfunction, the pharmacokinetic profile of a single dose of tigecycline does not change. In moderate and severe disorders (classes B and C on the Child-Pugh scale), the clearance of tigecycline decreases by 25% and 55%, respectively, the half-life increases by 23% and 43%;
- renal failure: with creatinine clearance less than 30 ml / min, including during hemodialysis, the pharmacokinetic profile of a single dose of tigecycline does not change. In severe renal failure, the AUC is 30% higher than in healthy volunteers.
Indications for use
- community-acquired pneumonia;
- complicated intra-abdominal infections;
- complicated infections of the skin and soft tissues.
Contraindications
The use of Tigacil is contraindicated in case of known hypersensitivity to its components or other antibiotics of the tetracycline group.
The drug should be used with caution in patients with severe hepatic impairment.
Tigacil, instructions for use: method and dosage
The antibiotic Tigacil is intended for intravenous drip infusion lasting 30-60 minutes.
The initial recommended dose for adults is 100 mg. Further, the drug is prescribed at 50 mg. The intervals between injections are 12 hours.
The doctor determines the duration of treatment individually, depending on the localization and severity of the infectious process, as well as the clinical response to Tigacil. Therapy for community-acquired pneumonia lasts from 7 to 14 days, complicated intra-abdominal infections, skin and soft tissue infections - from 5 to 14 days.
Rules for the preparation and administration of the infusion solution
Before the introduction into the vial with the lyophilisate, add 5.3 ml of NaCl (sodium chloride) 0.9% solution, or Ringer's lactate solution, or 5% dextrose solution, and gently rotate the vial until the powder is completely dissolved. In this case, the concentration of tigecycline in the finished solution is 10 mg / ml (in one bottle, 5 ml of a ready-to-administration solution containing 50 mg of tigecycline and a 6% excess of the drug is obtained).
Next, 5 ml of the solution is transferred into a vial with a 100 ml infusion solution (for a dose of 50 mg, a ready-made solution is taken from one vial, for a dose of 100 mg - from two vials).
The final infusion solution should have a maximum concentration of not more than 1 mg / ml, yellow or orange. It is not allowed to use a solution if it has a different color or contains visible inclusions.
Tigacil is administered through a separate infusion set or a T-shaped catheter. If several drugs are sequentially administered to the patient through the catheter, before the administration of Tigacil it should be washed with NaCl 0.9% solution, Ringer's lactate solution or 5% dextrose solution. It is imperative to take into account the compatibility of tigecycline with other drugs administered through the same catheter.
Side effects
- from the digestive system: very often (≥ 1/10) - nausea, vomiting, diarrhea; often (from ≥ 1/100 to <1/10) - dyspepsia, abdominal pain, anorexia; sometimes (from ≥ 1/1000 to <1/100) - hyperbilirubinemia, jaundice, increased activity of liver enzymes, acute pancreatitis; in isolated cases (spontaneous post-marketing messages) - severe liver dysfunction, liver failure;
- on the part of the cardiovascular system: often - phlebitis; sometimes - thrombophlebitis;
- on the part of the hematopoietic system: sometimes - eosinophilia; in isolated cases - thrombocytopenia;
- on the part of the blood coagulation system: often - an increase in the activated partial thromboplastin time, prothrombin time or INR (international normalized ratio);
- from the reproductive system: sometimes - vaginitis, vaginal candidiasis, leukorrhea;
- from the central nervous system: often - dizziness;
- dermatological and allergic reactions: often - itching, rash; in isolated cases - anaphylactic / anaphylactoid reactions;
- on the part of laboratory parameters: often - hypoproteinemia, increased activity of amylase and alkaline phosphatase in serum, increased blood urea nitrogen; sometimes - hyponatremia, hypocalcemia, hypoglycemia, increased creatinine in the blood;
- local reactions: sometimes - pain, swelling, inflammation and phlebitis at the injection site of Tigacil;
- others: often - delayed wound healing, asthenia, headache; sometimes chills.
The most common side effects, due to the development of which it was necessary to interrupt drug therapy, are nausea and vomiting.
Overdose
There is no information on Tigacil overdose.
A 60-minute infusion of 300 mg tigecycline in healthy volunteers increased the incidence of nausea and vomiting.
Hemodialysis is ineffective. Treatment is symptomatic.
special instructions
The use of the antibiotic Tigacil is recommended after microbiological identification of the pathogen and determination of its sensitivity to tigecycline. Until the results of microbiological tests are obtained, the drug can be used for empirical antibacterial monotherapy.
In hospital-acquired pneumonia, the effectiveness of the drug in clinical trials has not been established.
Tigacil belongs to the class of glycylcycline, structurally similar to tetracyclines, therefore, it can cause negative reactions similar to those when using antibiotics of the tetracycline series. These include: pancreatitis, intracranial hypertension, increased photosensitivity, as well as anti-anabolic action, which leads to an increase in the level of urea in the blood, the development of acidosis, azotemia and hypophosphatemia. For this reason, the drug should be used with caution in patients with established hypersensitivity to tetracycline antibiotics.
If the results of liver tests change during the period of therapy, careful medical supervision is required in order to identify signs of possible liver dysfunction in time and assess the balance of risks and benefits of continuing the use of Tigacil. It should be borne in mind that disorders can develop after the end of the course of treatment.
Like virtually all antibiotics, Tigacil can cause Clostridium difficile-associated diarrhea. If this diagnosis is suspected or confirmed, the drug is canceled and appropriate therapy is performed.
While taking tigecycline, pseudomembranous colitis may develop, which should be taken into account in differential diagnosis if diarrhea occurs during or after treatment.
Approximately 50% of tigecycline is excreted in the bile, therefore, special supervision during antibiotic therapy is required in patients with cholestasis.
Tigacil, used during the formation of teeth, can lead to a change in their color to gray, yellow, brown. For this reason, the drug at this time can be used only if other drugs are contraindicated or proved to be ineffective.
For complicated intra-abdominal infections due to intestinal perforation and with incipient sepsis or septic shock, Tigacil is usually used as part of a combination antibiotic therapy.
Against the background of taking an antibiotic, excessive growth of insensitive microorganisms is possible, therefore, the treatment process should be monitored by a doctor. In case of development of superinfection, appropriate therapy is carried out.
Experience in treating infections with tigecycline is limited in patients with severe comorbidities.
Influence on the ability to drive vehicles and complex mechanisms
Special studies to study the effect of Tigacil on human cognitive and psychomotor functions have not been conducted. Consideration should be given to the likelihood of dizziness, which affects the ability to perform potentially hazardous work, including driving and driving complex mechanisms.
Application during pregnancy and lactation
During pregnancy, Tigacil can only be used for health reasons, when the benefits to the woman definitely outweigh the risks to the fetus. There is no experience with the drug during childbirth.
It is not known whether tigecycline is excreted in breast milk. If treatment is necessary during lactation, it is recommended that breastfeeding be discontinued.
Pediatric use
In the treatment of children and adolescents under 18 years of age, Tigacil is not used due to the lack of data on the safety and efficacy of tigecycline in patients of this age group.
With impaired renal function
No dose adjustment is required in patients with renal insufficiency, including those on hemodialysis.
For violations of liver function
In mild and moderate hepatic impairment (classes A and B on the Child-Pugh scale), there is no need to change the dose of the drug.
Tigacil should be used with caution in the treatment of patients with severe hepatic impairment (class C on the Child-Pugh scale). The initial dose is 100 mg, in the future it is recommended to reduce it to 25 mg at the frequency of administration of the drug 2 times a day (at intervals of 12 hours). During the period of therapy, patients should be under close medical supervision.
Use in the elderly
Elderly patients do not need to adjust the dose of Tigacil.
Drug interactions
The cytochrome P450 system is not involved in the metabolism of tigecycline, therefore, drugs that induce or suppress the activity of isoenzymes of this system cannot affect the clearance of Tigacil. Tigecycline, in turn, should theoretically not change the degree of metabolism of these drugs.
With the simultaneous use of tigecycline (in a therapeutic dose) with digoxin (in an initial daily dose of 0.5 mg and subsequent doses of 0.25 mg), there were no changes in the pharmacokinetic profile of tigecycline, nor changes in the degree and rate of absorption and clearance of digoxin.
In vitro studies have not revealed antagonism between tigecycline and commonly used antibiotics of other groups.
Tigacil reduces the clearance and AUC of warfarin, can increase both the prothrombin time or the international normalized ratio, and the activated partial thromboplastin time. For this reason, when using the drug against the background of anticoagulant therapy, it is necessary to carefully monitor the results of coagulation tests. Warfarin does not affect the pharmacokinetics of tigecycline.
Like other antibiotics, tigecycline can reduce the effectiveness of oral contraceptives.
Tigacil is compatible with the following solutions: NaCl 0.9%, Ringer's lactate, dextrose 5%. When an antibiotic is administered through a T-shaped catheter, the solution obtained after diluting the lyophilisate of tigecycline in 0.9% NaCl solution or 5% dextrose solution is compatible with Ringer's solution of lactate, lidocaine hydrochloride, morphine, dopamine hydrochloride, dobutamine, ranitidine hydrochloride, calia, gentami chloride, tobramycin, metoclopramide, propofol, norepinephrine, haloperidol, amikacin, theophylline and piperacillin-tazobactam in dosage forms containing ethylenediaminetetraacetic acid.
When used through a T-shaped catheter, Tigacil is incompatible with omeprazole, esomeprazole, diazepam, amphotericin B and liposomal amphotericin B.
Analogs
Tigacil analogs are Vidoccin, Doxycycline, Doxycycline hydrochloride, Xedocin, Minolexin, Tetracycline, Unidox Solutab, etc.
Terms and conditions of storage
Store at temperatures up to 25 ° C out of reach of children.
The shelf life is 1.5 years.
The diluted lyophilisate can be stored at room temperature for no more than 24 hours: up to 6 hours - the solution in the vial after the first dilution, the remaining time - the solution after the final dilution. The final diluted solution can be stored for up to 48 hours at 2–8 ° C (refrigerated).
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Tigatsil
On specialized medical sites and forums, there are no reviews about Tigacil, which would allow assessing the degree of its effectiveness and tolerance.
The price of Tigacil in pharmacies
The approximate price of Tigatsil is 27,189-29,611 rubles. for 10 bottles.
Tigacil: prices in online pharmacies
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Drug name Price Pharmacy |
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Tigacil 50 mg lyophilisate for preparation of solution for infusion 10 pcs. 20173 RUB Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
